What the FDA labels say about taking them together
Methadone and phenobarbital
Methadone's FDA label of December 8, 2025 names phenobarbital in its drug interactions section; phenobarbital's label does not name methadone itself but warns about its class (Opioids (opioid agonists)). The methadone label: “The concomitant use of DISKETS Dispersible Tablets and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms in …”
Check it at the source: the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC); the phenobarbital FDA label on DailyMed (effective August 27, 2026).
What does the methadone label say about phenobarbital?
Methadone label, drug interactionsClinical Impact: The concomitant use of methadone hydrochloride tablets and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent on methadone. … for signs of respiratory depression and sedation. Rifampin, carbamazepine, phenytoin, St. John’s Wort, Phenobarbital Benzodiazepines and other Central Nervous System (CNS) Depressants
Source: FDA drug label (Diskets, NDA017058), Hikma Pharmaceuticals USA Inc., effective December 1, 2025 (SPL set e6af84de-cbfc-4a3b-bd73-6bcf77337168), via openFDA
Source: FDA drug label (Methadose, NDA017116), SpecGx LLC, effective April 27, 2026 (SPL set 808a9d0b-720b-4034-a862-5122ff514608), via openFDA
Source: FDA drug label (Methadone Hydrochloride, NDA021624), Mylan Institutional LLC, effective December 31, 2025 (SPL set 092d78eb-6423-495c-bf0d-e6532bea7138), via openFDA
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), via openFDA; the full label on DailyMed
What does the phenobarbital label say about methadone?
Phenobarbital's label does not name methadone itself; it warns about its class (Opioids (opioid agonists)):
Phenobarbital label, boxed warningDEPENDENCE AND WITHDRAWAL REACTIONS AFTER USE OF SEZABY FOR A LONGER DURATION THAN RECOMMENDED; and ABUSE, MISUSE AND ADDICTION WITH UNAPPROVED USE IN ADOLESCENTS AND ADULTS Risks from Concomitant Use with Opioids Concomitant use of phenobarbital products, including SEZABY, and opioids may result in profound sedation, respiratory depression, coma, and death.
Phenobarbital label, boxed warningConcomitant use of phenobarbital products, including SEZABY, and opioids may result in profound sedation, respiratory depression, coma, and death.
Source: FDA drug label (Phenobarbital), Chartwell RX, LLC, effective August 27, 2026 (SPL set 74428144-fb24-40a5-a670-3b876e2d116c), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Methadone | Phenobarbital | |
|---|---|---|
| Labeled for | Pain, Opioid use disorder | Seizures and epilepsy |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.177 per tablet 10 mg tablet | $0.213 per tablet 100 mg tablet |
| Shortage now | No current entry | A presentation being discontinued |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once